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1دورية أكاديمية
المؤلفون: Amanda F. Amaral, Bryan E. McQueen, Kimberly Bellingham-Johnstun, Taylor B. Poston, Toni Darville, Uma M. Nagarajan, Caroline Laplante, Tobias Käser
المصدر: Pathogens, Vol 10, Iss 10, p 1270 (2021)
مصطلحات موضوعية: Chlamydia trachomatis, porcine oviduct epithelial cell, developmental cycle, innate immune response, claudin-4, tight junctions, Medicine
الوصف: Chlamydia trachomatis (Ct) causes the most prevalent bacterial sexually transmitted disease leading to ectopic pregnancy and infertility. Swine not only have many similarities to humans, but they are also susceptible to Ct. Despite these benefits and the ease of access to primary tissue from this food animal, in vitro research in swine has been underutilized. This study will provide basic understanding of the Ct host–pathogen interactions in porcine oviduct epithelial cells (pOECs)—the counterparts of human Fallopian tube epithelial cells. Using NanoString technology, flow cytometry, and confocal and transmission-electron microscopy, we studied the Ct developmental cycle in pOECs, the cellular immune response, and the expression and location of the tight junction protein claudin-4. We show that Ct productively completes its developmental cycle in pOECs and induces an immune response to Ct similar to human cells: Ct mainly induced the upregulation of interferon regulated genes and T-cell attracting chemokines. Furthermore, Ct infection induced an accumulation of claudin-4 in the Ct inclusion with a coinciding reduction of membrane-bound claudin-4. Downstream effects of the reduced membrane-bound claudin-4 expression could potentially include a reduction in tight-junction expression, impaired epithelial barrier function as well as increased susceptibility to co-infections. Thereby, this study justifies the investigation of the effect of Ct on tight junctions and the mucosal epithelial barrier function. Taken together, this study demonstrates that primary pOECs represent an excellent in vitro model for research into Ct pathogenesis, cell biology and immunity.
وصف الملف: electronic resource
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2
المؤلفون: Breanna J. Turman, Damir Alzhanov, Uma M. Nagarajan, Toni Darville, Catherine M. O’Connell
المصدر: Infection and Immunity. 91
مصطلحات موضوعية: Infectious Diseases, Immunology, Parasitology, Microbiology
الوصف: Chlamydia trachomatis is the most common cause of infectious blindness and sexually transmitted bacterial infection globally. C. trachomatis contains a conserved chlamydial plasmid with eight coding sequences. Plasmid-cured Chlamydia strains are attenuated and display reduced infectivity in cell culture and in vivo genital infection of female mice.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::46cebbba83d4b9a368bc0a5ea8f0c4e8Test
https://doi.org/10.1128/iai.00392-22Test -
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المؤلفون: Crescentia Cho, Uma M. Nagarajan, Ian Huntress, Hayden N. Brochu, Erin Harrell, J. Ashley Ezzell, Shanmugam Nagarajan, Clare E. Gyorke, Xinxia Peng
المصدر: J Infect Dis
مصطلحات موضوعية: Chlamydia muridarum, Programmed cell death, Alpha (ethology), Mice, Interleukin-1alpha, Pelvic Inflammatory Disease Supplement, medicine, Animals, Immunology and Allergy, Receptor, Chlamydia, Cell Death, biology, Tumor Necrosis Factor-alpha, Interleukin, Epithelial Cells, Chlamydia Infections, biology.organism_classification, medicine.disease, Epithelium, Mice, Inbred C57BL, Infectious Diseases, medicine.anatomical_structure, Cancer research, Female, Tumor necrosis factor alpha
الوصف: Chlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other’s downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::012647aff0a4db7389803e01e00eb424Test
https://doi.org/10.1093/infdis/jiab168Test -
4
المؤلفون: Branimir Popovic, Pamelia E. Fraungruber, Uma M. Nagarajan, Ramona L. Burris, Catherine L. Haggerty, James D. Sikes, Rajneesh Jha, Shanmugam Nagarajan, Leah Hennings
المصدر: Atherosclerosis
مصطلحات موضوعية: 0301 basic medicine, Apolipoprotein E, Chlamydia muridarum, Chemokine, Time Factors, Mice, Knockout, ApoE, medicine.medical_treatment, Aortic Diseases, Hyperlipidemias, Inflammation, 030204 cardiovascular system & hematology, Reproductive Tract Infections, Article, 03 medical and health sciences, 0302 clinical medicine, Aortic sinus, medicine, Animals, Cells, Cultured, Chlamydia, biology, business.industry, Macrophages, Uterus, Chlamydia Infections, Atherosclerosis, biology.organism_classification, medicine.disease, Plaque, Atherosclerotic, Disease Models, Animal, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Receptors, LDL, LDL receptor, Immunology, Disease Progression, biology.protein, Cytokines, Female, lipids (amino acids, peptides, and proteins), Inflammation Mediators, medicine.symptom, Cardiology and Cardiovascular Medicine, business
الوصف: Background and aims Atherosclerosis is a chronic inflammatory disease, and recent studies have shown that infection at remote sites can contribute to the progression of atherosclerosis in hyperlipidemic mouse models. In this report, we tested the hypothesis that genital Chlamydia infection could accelerate the onset and progression of atherosclerosis. Methods Apolipoprotein E (Apoe−/−) and LDL receptor knockout (Ldlr−/−) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses were assessed and quantified. Results Compared to the uninfected groups, infected Apoe−/− and Ldlr−/− mice developed significantly more atherosclerotic lesions in the aortic sinus and in the descending aorta. Increased lesions were associated with higher circulating levels of serum amyloid A-1, IL-1β, TNF-α, and increased VCAM-1 expression in the aortic sinus, suggesting an association with inflammatory responses observed during C. muridarum infection. Genital infection courses were similar in Apoe−/−, Ldlr−/−, and wild type mice. Further, Apoe−/− mice developed severe uterine pathology with increased dilatations. Apoe-deficiency also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could have contributed to the genital pathology in Apoe−/− mice. Conclusions Overall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::070cd49247b5268c39b33531fb46d914Test
https://doi.org/10.1016/j.atherosclerosis.2019.09.021Test -
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المؤلفون: Uma M. Nagarajan, Catherine M. O'Connell, M. Leslie Fulcher, Kate Patton, Bryan E. McQueen, Scott H. Randell, Mehmet Kesimer, Emily Powell, Amy Kiatthanapaiboon, Mariam Lam, Priscilla B. Wyrick, Boris Reidel, Victoria J. Madden, Avinash Kollipara, Toni Darville, Robert J. Suchland
المصدر: Infect Immun
مصطلحات موضوعية: 0301 basic medicine, Cellular differentiation, T-Lymphocytes, Cell, Chlamydia trachomatis, 0302 clinical medicine, Chemokine CCL5, Receptors, Interferon, Host Response and Inflammation, Chlamydia, medicine.diagnostic_test, Intercellular Adhesion Molecule-1, Cell biology, Infectious Diseases, medicine.anatomical_structure, Female, Adult, Amino Acid Transport System ASC, Fusion Regulatory Protein 1, Heavy Chain, T cell, Immunology, Primary Cell Culture, Vascular Cell Adhesion Molecule-1, Biology, Microbiology, Models, Biological, Flow cytometry, Minor Histocompatibility Antigens, 03 medical and health sciences, Salpingectomy, Antigens, CD, Receptors, Transferrin, medicine, CXCL10, Humans, Fallopian Tubes, Host Microbial Interactions, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Epithelial Cells, Chlamydia Infections, medicine.disease, Epithelium, Chemokine CXCL11, Chemokine CXCL10, 030104 developmental biology, Gene Expression Regulation, Parasitology, Biomarkers, 030215 immunology, Fallopian tube
الوصف: Chlamydia trachomatis infection of the human fallopian tubes can lead to damaging inflammation and scarring, ultimately resulting in infertility. To study the human cellular responses to chlamydial infection, researchers have frequently used transformed cell lines that can have limited translational relevance. We developed a primary human fallopian tube epithelial cell model based on a method previously established for culture of primary human bronchial epithelial cells. After protease digestion and physical dissociation of excised fallopian tubes, epithelial cell precursors were expanded in growth factor-containing medium. Expanded cells were cryopreserved to generate a biobank of cells from multiple donors and cultured at an air-liquid interface. Culture conditions stimulated cellular differentiation into polarized mucin-secreting and multiciliated cells, recapitulating the architecture of human fallopian tube epithelium. The polarized and differentiated cells were infected with a clinical isolate of C. trachomatis, and inclusions containing chlamydial developmental forms were visualized by fluorescence and electron microscopy. Apical secretions from infected cells contained increased amounts of proteins associated with chlamydial growth and replication, including transferrin receptor protein 1, the amino acid transporters SLC3A2 and SLC1A5, and the T-cell chemoattractants CXCL10, CXCL11, and RANTES. Flow cytometry revealed that chlamydial infection induced cell surface expression of T-cell homing and activation proteins, including ICAM-1, VCAM-1, HLA class I and II, and interferon gamma receptor. This human fallopian tube epithelial cell culture model is an important tool with translational potential for studying cellular responses to Chlamydia and other sexually transmitted pathogens.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c43f273846a11a5bd2778903f6324a9Test
https://europepmc.org/articles/PMC7440757Test/ -
6دورية أكاديمية
المؤلفون: Uma M. Nagarajan, Alyssa Bushey, Jeremy M. Boss, Email Alerts
المساهمون: The Pennsylvania State University CiteSeerX Archives
الوصف: This article cites 50 articles, 23 of which you can access for free at
وصف الملف: application/pdf
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المؤلفون: Uma M. Nagarajan, Clare E. Gyorke, Yugen Zhang, Avinash Kollipara, John A. Allen, J. Ashley Ezzell, Toni Darville, Stephanie A. Montgomery
المصدر: Journal of immunology (Baltimore, Md. : 1950). 205(11)
مصطلحات موضوعية: CD4-Positive T-Lymphocytes, Pathology, medicine.medical_specialty, Chlamydia muridarum, animal structures, Immunology, Interleukin-1beta, Cervix Uteri, Oviducts, Reproductive Tract Infections, Proinflammatory cytokine, 03 medical and health sciences, Mice, 0302 clinical medicine, Fibrosis, Interleukin-1alpha, medicine, Immunology and Allergy, Animals, Cervix, biology, business.industry, Uterine horns, Genitalia, Female, Chlamydia Infections, medicine.disease, biology.organism_classification, Mice, Inbred C57BL, CXCL2, Disease Models, Animal, medicine.anatomical_structure, Neutrophil Infiltration, Oviduct, Female, business, 030215 immunology, Fallopian tube
الوصف: Chlamydia trachomatis infection of the female genital tract can lead to irreversible fallopian tube scarring. In the mouse model of genital infection using Chlamydia muridarum, IL-1R signaling plays a critical role in oviduct tissue damage. In this study, we investigated the pathologic role of IL-1α, one of the two proinflammatory cytokines that bind to IL-1R. Il1a−/− mice infected with C. muridarum cleared infection at their cervix at the same rate as wild-type (WT) mice, but were significantly protected from end point oviduct damage and fibrosis. The contribution of IL-1α to oviduct pathology was more dramatic than observed in mice deficient for IL-1β. Although chlamydial burden was similar in WT and Il1a−/− oviduct during peak days of infection, levels of IL-1β, IL-6, CSF3, and CXCL2 were reduced in Il1a−/− oviduct lysates. During infection, Il1a−/− oviducts and uterine horns exhibited reduced neutrophil infiltration, and this reduction persisted after the infection resolved. The absence of IL-1α did not compromise CD4 T cell recruitment or function during primary or secondary chlamydial infection. IL-1α is expressed predominantly by luminal cells of the genital tract in response to infection, and low levels of expression persisted after the infection cleared. Ab-mediated depletion of IL-1α in WT mice prevented infection-induced oviduct damage, further supporting a key role for IL-1α in oviduct pathology.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c417699c518bbece271320f3b36e5facTest
https://pubmed.ncbi.nlm.nih.gov/33087404Test -
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المؤلفون: Uma M. Nagarajan, John A. Allen, Angela Lovett, Manoj K. Tripathy, Yugen Zhang, Stephanie A. Montgomery, Clare E. Gyorke
المصدر: Infection and Immunity. 87
مصطلحات موضوعية: Pathology, medicine.medical_specialty, animal structures, Chlamydia, Transgene, Immunology, Uterus, Caspase-11, Biology, medicine.disease_cause, medicine.disease, biology.organism_classification, Microbiology, Infectious Diseases, medicine.anatomical_structure, medicine, Oviduct, Parasitology, Chlamydia trachomatis, Chlamydia muridarum, Pathogen
الوصف: It has been shown that caspase-1, but not its upstream activator, ASC, contributes to oviduct pathology during mouse genital Chlamydia muridarum infection. We hypothesized that this dichotomy is due to the inadvertent absence of caspase-11 in previously used caspase-1-deficient mice. To address this, we studied the independent contributions of caspase-1 and -11 during genital Chlamydia infection. Our results show that caspase-11 deficiency was sufficient to recapitulate the effect of the combined absence of both caspase-1 and caspase-11 on oviduct pathology. Further, mice that were deficient for both caspase-1 and -11 but that expressed caspase-11 as a transgene (essentially, caspase-1-deficient mice) had no significant difference in oviduct pathology from control mice. Caspase-11-deficient mice showed reduced dilation in both the oviducts and uterus. To determine the mechanism by which caspase-11-deficient mice developed reduced pathology, the chlamydial burden and immune cell infiltration were determined in the oviducts. In the caspase-11-deficient mice, we observed increased chlamydial burdens in the upper genital tract, which correlated with increased CD4 T cell recruitment, suggesting a contribution of caspase-11 in infection control. Additionally, there were significantly fewer neutrophils in the oviducts of caspase-11-deficient mice, supporting the observed decrease in the incidence of oviduct pathology. Therefore, caspase-11 activation contributes to pathogen control and oviduct disease independently of caspase-1 activation.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b83ca09cb57b00c74c8cda93b85dadc7Test
https://doi.org/10.1128/iai.00262-19Test -
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المؤلفون: Taylor B. Poston, Toni Darville, Kimberly Bellingham-Johnstun, Tobias Käser, Uma M. Nagarajan, Caroline Laplante, Amanda F. Amaral, Bryan E. McQueen
المصدر: Pathogens, Vol 10, Iss 1270, p 1270 (2021)
Pathogens
Volume 10
Issue 10مصطلحات موضوعية: Microbiology (medical), Sexually transmitted disease, Chemokine, tight junctions, developmental cycle, Chlamydia trachomatis, medicine.disease_cause, Article, Immune system, Interferon, medicine, Immunology and Allergy, Molecular Biology, Innate immune system, General Immunology and Microbiology, Tight junction, biology, porcine oviduct epithelial cell, Cell biology, Infectious Diseases, claudin-4, innate immune response, biology.protein, Medicine, Oviduct, medicine.drug
الوصف: Chlamydia trachomatis (Ct) causes the most prevalent bacterial sexually transmitted disease leading to ectopic pregnancy and infertility. Swine not only have many similarities to humans, but they are also susceptible to Ct. Despite these benefits and the ease of access to primary tissue from this food animal, in vitro research in swine has been underutilized. This study will provide basic understanding of the Ct host–pathogen interactions in porcine oviduct epithelial cells (pOECs)—the counterparts of human Fallopian tube epithelial cells. Using NanoString technology, flow cytometry, and confocal and transmission-electron microscopy, we studied the Ct developmental cycle in pOECs, the cellular immune response, and the expression and location of the tight junction protein claudin-4. We show that Ct productively completes its developmental cycle in pOECs and induces an immune response to Ct similar to human cells: Ct mainly induced the upregulation of interferon regulated genes and T-cell attracting chemokines. Furthermore, Ct infection induced an accumulation of claudin-4 in the Ct inclusion with a coinciding reduction of membrane-bound claudin-4. Downstream effects of the reduced membrane-bound claudin-4 expression could potentially include a reduction in tight-junction expression, impaired epithelial barrier function as well as increased susceptibility to co-infections. Thereby, this study justifies the investigation of the effect of Ct on tight junctions and the mucosal epithelial barrier function. Taken together, this study demonstrates that primary pOECs represent an excellent in vitro model for research into Ct pathogenesis, cell biology and immunity.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6febdaae427f1ad4c714e3244fce9449Test
https://doi.org/10.3390/pathogens10101270Test -
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المؤلفون: Taylor B. Poston, McKensie Wall, Catherine M. O'Connell, Ali N. Russell, Yanyan Qu, Toni Darville, Uma M. Nagarajan, Lauren C. Frazer, Jenna Girardi
المصدر: The Journal of Immunology. 199:2845-2854
مصطلحات موضوعية: 0301 basic medicine, Adoptive cell transfer, Cellular immunity, biology, Effector, T cell, Immunology, medicine.disease_cause, biology.organism_classification, Virology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Antigen, Monoclonal, medicine, Immunology and Allergy, Chlamydia trachomatis, Chlamydia muridarum, 030215 immunology
الوصف: Chlamydia is responsible for millions of new infections annually, and current efforts focus on understanding cellular immunity for targeted vaccine development. The Chlamydia-specific CD4 T cell response is characterized by the production of IFN-γ, and polyfunctional Th1 responses are associated with enhanced protection. A major limitation in studying these responses is the paucity of tools available for detection, quantification, and characterization of polyfunctional Ag-specific T cells. We addressed this problem by developing a TCR-transgenic (Tg) mouse with CD4 T cells that respond to a common Ag in Chlamydia muridarum and Chlamydia trachomatis. Using an adoptive-transfer approach, we show that naive Tg CD4 T cells become activated, proliferate, migrate to the infected tissue, and acquire a polyfunctional Th1 phenotype in infected mice. Polyfunctional Tg Th1 effectors demonstrated enhanced IFN-γ production compared with polyclonal cells, protected immune-deficient mice against lethality, mediated bacterial clearance, and orchestrated an anamnestic response. Adoptive transfer of Chlamydia-specific CD4 TCR-Tg T cells with polyfunctional capacity offers a powerful approach for analysis of protective effector and memory responses against chlamydial infection and demonstrates that an effective monoclonal CD4 T cell response may successfully guide subunit vaccination strategies.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::ec198a1b4e48bba3c547472ed31dff85Test
https://doi.org/10.4049/jimmunol.1700914Test
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